Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, 16, De Crespigny Park, London-SE5 8AF, UK.
Mental Health of Older Adults and Dementia Clinical Academic Group, South London and Maudsley NHS foundation Trust, 115, Denmark Hill, London-SE5 8AQ, UK.
Acta Neuropsychiatr. 2020 Feb;32(1):10-22. doi: 10.1017/neu.2019.28. Epub 2019 Aug 27.
Cognitive impairment and depression are among the most prevalent and most disabling non-motor symptoms in Parkinson's disease (PD). The genetic factors that are associated with these symptoms remain uncertain. This systematic review aims to summarise the prevailing evidence from all genetic association studies investigating the genetic variants associated with cognitive impairment and depressive symptoms in people with PD.
A systematic review using five online databases: PubMed, PsycINFO, CINAHL, EMBASE and OpenGrey (PROSPERO protocol: CRD42017067431). We completed the quality assessment using the Q-Genie tool.
2353 articles were screened, and 43 articles were found to be eligible to be included. A meta-analysis of studies investigating LRRK2 rs34637584 confirmed that the minor allele carriers had significantly less cognitive impairment (p = 0.015). Further meta-analyses showed that GBA variants rs76763715 (p < 0.001) and rs421016 (p = 0.001) were significantly associated with more cognitive impairment in people with PD. Minor alleles of GBA variants rs76763715, rs421016, rs387906315 and rs80356773 were associated with more depressive symptoms in PD. Moreover, APOE ε4 allele has been associated with more cognitive impairment in PD. BDNF (rs6265) and CRY1 (rs2287161) variants have been associated with more depressive symptoms in people with PD.
PD carriers of GBA variants are at high risk for cognitive decline and depression. Screening for these variants may facilitate early identification and effective management of these non-motor symptoms. The molecular mechanisms underlying favourable cognitive functioning in LRRK2 rs34637584 variant carriers warrant further investigation.
认知障碍和抑郁是帕金森病（PD）中最常见和最具致残性的非运动症状之一。与这些症状相关的遗传因素仍不确定。本系统综述旨在总结所有遗传关联研究的现有证据，这些研究调查了与 PD 患者认知障碍和抑郁症状相关的遗传变异。
使用五个在线数据库（PubMed、PsycINFO、CINAHL、EMBASE 和 OpenGrey（PROSPERO 方案：CRD42017067431））进行系统综述。我们使用 Q-Genie 工具完成了质量评估。
筛选了 2353 篇文章，发现 43 篇文章符合纳入标准。对研究 LRRK2 rs34637584 的研究进行荟萃分析证实，携带次要等位基因的患者认知障碍明显较轻（p = 0.015）。进一步的荟萃分析表明，GBA 变体 rs76763715（p < 0.001）和 rs421016（p = 0.001）与 PD 患者的认知障碍明显相关。GBA 变体 rs76763715、rs421016、rs387906315 和 rs80356773 的次要等位基因与 PD 中的更多抑郁症状相关。此外，APOE ε4 等位基因与 PD 中的更多认知障碍相关。BDNF（rs6265）和 CRY1（rs2287161）变体与 PD 患者的更多抑郁症状相关。
GBA 变体的 PD 携带者认知能力下降和抑郁的风险较高。对这些变体进行筛查可能有助于早期识别和有效管理这些非运动症状。LRRK2 rs34637584 变体携带者有利认知功能的潜在分子机制值得进一步研究。
